National Academy of Sciences
Allergy (and clinical immunology)
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Ressources et Actualités pour la spécialité Allergie
Curated by
Gilbert C FAURE
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Oral food challenge (OFC) is the gold-standard to diagnose food allergy; however, it is a labour and resource-intensive procedure with the risk of causing an acute allergic reaction, which is potentially severe. Therefore, OFC are reserved for cases where the clinical history and the results of skin prick test and/or specific IgE do not confirm or exclude the diagnosis of food allergy. This is a significant proportion of patients seen in Allergy clinics and results in a high demand for OFC. The basophil activation test (BAT) has emerged as a new diagnostic test for food allergy. With high diagnostic accuracy, it can be particularly helpful in the cases where skin prick test and specific IgE are equivocal and may allow reducing the need for OFC. BAT has high specificity, which confers a high degree of certainty in confirming the diagnosis of food allergy and allows deferring the performance of OFC in patients with a positive BAT. The diagnostic utility of BAT is allergen-specific and needs to be validated for different allergens and in specific patient populations. Standardisation of the laboratory methodology and of the data analyses would help to enable a wider clinical application of BAT. Via Marcelo de Carvalho Bittencourt 
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Nature Communications | doi:10.1038/ncomms11610
Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystalstructure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure revealsthe mechanism of omalizumab-mediated inhibition of IgE interactions with both high- andlow-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. Thestructure of the complex also provides mechanistic insight into a class of disruptive IgEinhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We usethis structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumabbinding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination withomalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistantIgE-Fc fragments on human basophils. This combination treatment also blocks basophilactivation more efficiently than either agent alone, providing a novel approach to proberegulatory mechanisms underlying IgE hypersensitivity with implications for therapeuticinterventions Via Krishan Maggon
Krishan Maggon 's curator insight,
May 28, 2016 10:25 AM
Published 19 May 2016 NATURE COMMUNICATIONS | 7:11610 | DOI: 10.1038/ncomms11610 | www.nature.com/naturecommunications ;
Structural basis of omalizumab therapy andomalizumab-mediated IgE exchange Luke F. Pennington1,2,3, Svetlana Tarchevskaya1,3, Daniel Brigger4,5, Karthik Sathiyamoorthy1,3,Michelle T. Graham3,6, Kari Christine Nadeau2,3,6, Alexander Eggel4,5& Theodore S. Jardetzky
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A new study using 5,000 stored blood samples found no increase in the presence of food-specific immunoglobulin E (IgE) -- a blood marker associated with food allergy -- in children's blood between the 1980s and the 2000s.
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The Natural History of Food Allergy. Resolution by age/peak food IgE level. @JACIInPractice. https://t.co/eNzUOXr2sK https://t.co/uc1Ln6N4Oy
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Researchers found immunoglobulin E-mediated food allergy in just half of observed children in a recent population based birth cohort study.Further, immunoglobulin E (IgE)-mediated food allergy showed different developmental risk factors...
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N Z Med J. 2016 Feb 19;129(1430):78-88.
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RT @FoodAllergy: “Patch” Clinical Trial for Peanut Allergy Now Recruiting https://t.co/t3NEtQ3qYN https://t.co/1GaKpYJkyK...
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ConclusionThe response to OIT was associated with significant increases in serum allergen‐specific IgG1 levels after rush phase and high baseline IgA levels, compared with small changes in immunoglobulin response in low‐responders.
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The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes.
Gilbert C FAURE's insight:
Results
Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens’ egg 2.7 % (1.6–3.8); cows’ milk 2.4 % (1.4–3.5); peanut 0.7 % (0.1–1.3); soy 0.4 % (0.0–0.8); wheat 0.2 % (0.0–0.5) and 0.1 % (0.0–0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens’ egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows’ milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction. ConclusionsJust under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes. OPEN
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Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours.
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Knowledge, practice, and views on precautionary allergen labeling for the management of IgE-mediated food allergy https://t.co/UqHSov5P9P
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Cross-linking of mast cell (MC) IgE receptors (FcεRI) triggers degranulation of secretory granules (SGs) and the release of many allergic and inflammatory mediators. Although degranulation depends crucially on microtubule dynamics, the molecular machinery that couples SGs to microtubule-dependent transport is poorly understood. In this study, we demonstrate that mice lacking Kif5b (the heavy chain of kinesin-1) in hematopoietic cells are less sensitive to IgE-mediated, passive, systemic anaphylaxis. After IgE-induced stimulation, bone marrow–derived MCs from Kif5b knockout mice exhibited a marked reduction in SG translocation toward the secretion site. In contrast, a lack of Kif5b did not affect cytokine secretion, early FcεRI-initiated signaling pathways, or microtubule reorganization upon FcεRI stimulation. We identified Slp3 as the critical effector linking kinesin-1 to Rab27b-associated SGs. Kinesin-1 recruitment to the Slp3/Rab27b effector complex was independent of microtubule reorganization but occurred only upon stimulation requiring phosphatidylinositol 3-kinase (PI3K) activity. Our findings demonstrate that PI3K-dependent formation of a kinesin-1/Slp3/Rab27b complex is critical for the microtubule-dependent movement of SGs required for MC degranulation.
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In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE.
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Clin Exp Allergy. 2015 Sep;45(9):1419-29. doi: 10.1111/cea.12566. Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Gilbert C FAURE's insight:
Abstract Allergic diseases and conditions are widespread and their incidence is on the increase. They are characterized by the activation of mast cells resident in tissues and the consequent infiltration and stimulation of several inflammatory cells, predominantly eosinophils. Cell–cell cross-talk and the release of mediators are responsible for the symptoms and for the modulation of the response. The gold standard of therapeutic intervention is still glucocorticosteroids, although they are not effective in all patients and may cause numerous side effects. Symptomatic medications are also widespread. As research has led to deeper insights into the mechanisms governing the diseases, new avenues have been opened resulting in recent years in the development of monoclonal antibodies (mAbs) such as anti-IgE mAbs (omalizumab) and others still undergoing clinical trials aimed to specifically target molecules involved in the migration and stimulation of inflammatory cells. In this review, we summarize new developments in the field of anti-allergic mAbs with special emphasis on the treatment of asthma, particularly severe forms of this condition, and atopic dermatitis, which are two unmet clinical needs.
Krishan Maggon 's curator insight,
April 18, 2016 9:31 AM
IUPHAR REVIEW
Monoclonal antibodies: the new magic bullets for allergy: IUPHAR Review 17 Authors N Landolina, F Levi-Schaffer First published: 1 February 2016Full publication history DOI: 10.1111/bph.13396
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ncbi.nlm.nih.gov - Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to devel...
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Case Rep Dermatol. 2016 Jan 27;8(1):10-3. doi: 10.1159/000443631.
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The Cloning and Expression of Human Monoclonal Antibodies: Implications for Allergen Immunotherapy https://t.co/Ppkm8zBCUf
Abstract Allergic responses are dependent on the highly specific effector functions of IgE antibodies. Conversely, antibodies that block the activity of IgE can mediate tolerance to allergen. Technologies that harness the unparalleled specificity of antibody responses have revolutionized the way that we diagnose and treat human disease. This area of research continues to advance at a rapid pace and has had a significant impact on our understanding of allergic disease. This review will present an overview of humoral responses and provide an up-to-date summary of technologies used in the generation of human monoclonal antibodies. The impact that monoclonal antibodies have on allergic disease will be discussed, with a particular focus on allergen immunotherapy, which remains the only form of treatment that can modulate the underlying immune mechanisms and induce long-term clinical tolerance. KeywordsHuman monoclonal antibodies Allergen immunotherapy B cells Cloning Human Allergy
Via Krishan Maggon
Krishan Maggon 's curator insight,
February 26, 2016 2:20 AM
Immunotherapy And Immunomodulators (B Vickery, Section Editor) Current Allergy and Asthma Reports February 2016, 16:15 First online: 16 January 2016 Open Access The Cloning and Expression of Human Monoclonal Antibodies: Implications for Allergen Immunotherapy Louisa K. James
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ConclusionThe storage proteins 11S globulin, 7S globulin and 2S albumin are “novel” allergens demonstrated in lemon seeds and homologous to the storage proteins in cashew.
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ConclusionsAge and sex should be taken into account when interpreting the results of skin tests and sIgE measurement, and age‐ and sex‐specific normative data are needed for these allergy tests.
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Read the latest article version by Dennis Ownby, Christine Cole Johnson, at F1000Research.
Gilbert C FAURE's insight:
Abstract
Allergic reactions to pets have been recognized for at least a hundred years. Yet our understanding of the effects of all of the interactions between pet exposures and human immune responses continues to grow. Allergists, epidemiologists, and immunologists have spent years trying to better understand how exposures to pet allergens lead to allergic sensitization (the production of allergen-specific immunoglobulin class E [IgE] antibodies) and subsequent allergic disease. A major new development in this understanding is the recognition that pet exposures consist of not only allergen exposures but also changes in microbial exposures. Exposures to certain pet-associated microbes, especially in the neonatal period, appear to be able to dramatically alter how a child’s immune system develops and this in turn reduces the risk of allergic sensitization and disease. An exciting challenge in the next few years will be to see whether these changes can be developed into a realistic preventative strategy with the expectation of significantly reducing allergic disease, especially asthma.
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Bertin Technologies worked with Genclis SAS to perfect the homogenization of cashew nuts in order to extract proteins recognized by IgE antibodies from aller...
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